Case Control Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2018; 6(13): 600-610
Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.600
Iron metabolism disorders in patients with hepatitis B-related liver diseases
Yan-Hang Gao, Jing-Yun Wang, Pei-Yan Liu, Jing Sun, Xiao-Mei Wang, Rui-Hong Wu, Xiu-Ting He, Zheng-Kun Tu, Chun-Guang Wang, Hong-Qin Xu, Jun-Qi Niu
Yan-Hang Gao, Jing-Yun Wang, Pei-Yan Liu, Jing Sun, Xiao-Mei Wang, Rui-Hong Wu, Hong-Qin Xu, Jun-Qi Niu, Department of Hepatology, The First Hospital of Jilin University, Jilin University, Changchun 130021, Jilin Province, China
Jing-Yun Wang, Department of Gastroenterology, Weihaiwei People’s Hospital, Weihai 264200, Shandong Province, China
Jing Sun, Department of Gastroenterology, Heping Hospital, Changzhi Medical College, Changzhi 046011, Shanxi Province, China
Xiu-Ting He, Department of Geriatrics, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Zheng-Kun Tu, Department of Translational Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Chun-Guang Wang, Department of Surgery, The Second Hospital of Jilin University, Changchun 130021, Jilin Province, China
Jun-Qi Niu, Jilin Provincial Key Laboratory of Infectious Diseases, Laboratory of Molecular Virology, Changchun 130021, Jilin Province, China
Author contributions: Niu JQ, Wang CG and Xu HQ designed the research; Niu JQ, Gao YH, Wang CG, Liu PY, Sun J, and He XT treated the patients and collected the materials and clinical data from patients; Wang JY, Wang XM, and Tu ZK performed the assays; Xu HQ analyzed the data; Gao YH and Xu HQ wrote the paper. Wang CG, Xu HQ, and Niu JQ are co-corresponding authors. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.
Supported by the National Science and Technology Major Project, No. 2014ZX10002002 and No. 2017ZX10202202; the National Key Research Plan “Precision Medicine Research” Key Project, No. 2017YFC0908103; the National Natural Science Foundation of China, No. 81700534; and Program for JLU Science and Technology Innovative Research Team, No. 2017TD-08.
Institutional review board statement: The study was reviewed and approved by the First Hospital Ethical Committee of Jilin University.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: Dataset available from the corresponding author at junqi_niu@163.com or hongqinxu86@jlu.edu.cn.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jun-Qi Niu, PhD, Professor, Department of Hepatology, First Hospital of Jilin University, No. 71, Xinmin Street, Changchun 130021, Jilin Province, China. junqi_niu@163.com
Telephone: +86-431-88783486 Fax: +86-431-85612468
Received: July 17, 2018
Peer-review started: July 17, 2018
First decision: August 25, 2018
Revised: September 16, 2018
Accepted: October 16, 2018
Article in press: October 16, 2018
Published online: November 6, 2018
Abstract
AIM

To investigate the relationship between levels of iron metabolism markers and hepatitis B virus (HBV)-related chronic liver diseases.

METHODS

This case-control study with 318 participants included 78 cases of chronic hepatitis B, 85 cases of HBV-related liver cirrhosis, 77 cases of HBV-related hepatocellular carcinoma, and 78 healthy controls. Markers of iron metabolism were detected in participants. Hematological and biochemical parameters and HBV-DNA were assessed. Child-Pugh grade and Barcelona Clinic Liver Cancer stage were determined for each hepatocellular carcinoma patient. Perls’ staining was performed on liver sections. The SPSS program was used for all statistical analyses, and statistical significance was considered if a P-value < 0.05.

RESULTS

Significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. Correlation analysis indicated that serum hepcidin was negatively correlated with HBV-DNA load (P < 0.01). Serum ferritin and transferrin saturation levels increased proportionally to the extent of liver cirrhosis and poorer Child-Pugh scores (P < 0.05). The decreased serum iron and transferrin saturation levels were significantly correlated with a smaller hepatocellular carcinoma tumor burden according to Barcelona Clinic Liver Cancer staging. Liver histology showed a clearly increasing trend in iron deposition in the liver tissues with increased fibrosis, which became prominent at stages 3 (severe liver fibrosis) and 4 (cirrhosis).

CONCLUSION

Iron metabolism disorders occur in patients with HBV-related liver diseases. The serum markers of iron metabolism disorders vary in different stages of HBV-related liver diseases.

Keywords: Hepatocellular carcinoma, Hepcidin, Iron staining, Hepatitis B, Liver fibrogenesis

Core tip: The relationship between hepatitis B viruses (HBV) related chronic liver diseases and levels of components in iron metabolism and the corresponding impact on liver disease severity have not been clearly described. In our study, we found that significantly higher serum ferritin and lower serum hepcidin levels were detected in all groups of HBV-infected patients compared with healthy controls. Serum iron, total iron binding capacity, and serum transferrin levels were significantly lower in patients with cirrhosis and hepatocellular carcinoma, whereas the hepcidin level was higher than that in chronic hepatitis B patients. In conclusion, iron metabolism disorders are present in patients with HBV-related liver diseases. The characteristics of iron metabolism disorders in different development stages of HBV-related liver diseases varied.